This invention is concerned with a novel process for converting biologically inactive cis-6-(substituted-arylethenyl)-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-on es to the anti-hypercholesterolemic trans-isomers by heating the cis-isomer with a heavy metal or salt thereof.
Belgian Pat. No. 867,421 discloses a group of synthetic compounds of the generic formula: ##STR1## in which E represents a direct bond, a C.sub.1-3 alkylene bridge or a vinylene bridge and the various R's represent a variety of substituents, which are anti-hypercholesterolemic agents by virtue of their ability to specifically inhibit HMG-CoA reductase, the enzyme which catalyzes the rate-limiting step in the biosynthesis of cholesterol.
Willard et al., U.S. Application Ser. No. 140,323, filed Apr. 14, 1980, now abandoned, discloses related compounds of generic structure: ##STR2## wherein A is hydrogen or methyl, E is a direct bond, a C.sub.1-3 alkylene bridge or a vinylene bridge and the R's represent a variety of substituents. The active stereoisomer is that depicted which is a 4-R-trans-isomer.
As with most synthetic procedures, the process employed by Willard et al., is not stereo-specific but ends up with a cis/trans-mixture, the components of which must be separated to produce the useful trans-isomer in a pure state and a similar quantity of the up to now, useless, cis-isomer.
Now with the present invention there is provided a novel process for converting these inactive cis-6-(substituted-arylethenyl)-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-on es to the biologically active trans-isomer. After isolating the trans-isomer from the resulting cis/trans-mixture, the remaining cis-isomer is recycled in the novel isomerization process of this invention.